Talking to Hameroff about the cytoskeleton makes you want to run into the streets and hand out pamphlets about this marvelous bio-invention. Here is a structure that should be a household word. It is a network nested within each neuron, which is itself nested within a larger neuronal net. The fractal beauty of this forest within a tree within a forest wasn’t lost on Hameroff, and he began to wonder if there wasn’t more to it. Perhaps the cytoskeletal net and the neuronal net are partners in the mind puzzle, working at different scales. Perhaps the tinier cytoskeletal net is the “secret basement” in the cognitive hierarchy, the root cellar of consciousness.
As Hameroff was finishing Hahnemann Medical School in Philadelphia and trying to decide what to specialize in, a professor told him that one of the effects of anesthesia was to cripple the microtubules in neurons. He now says, “That made me think. Is there a mechanism in microtubules that controls self-awareness, intuitive thought, emotion? Do microtubules help power consciousness?” Hameroff specialized in anesthesiology and began to read everything he could about the gas’s chilling effect on microtubules.
Another revelation came years later when colleague Rich Watt brought him an electron-microscope portrait of a tiny network and said, “What does this look like?” “Cytoskeleton,” Hameroff shot back, which made Watt smile. “Look again,” he said. “It’s a microprocessor, a computer chip.”
The eerie resemblance had a profound impact on Hameroff. “The structure of the cytoskeleton is not coincidental, I decided. And the fact that consciousness fades when the microtubule quiets is not coincidental. The cytoskeleton network is as parallel and as interconnected as the neuronal net, but a thousand times smaller. It contains millions to billions of cytoskeletal subunits per nerve cell! The cytoskeleton, I decided, is a lot more than mere cell scaffolding or a protoplasm traffic cop—it’s a full-fledged signaling network—a processor for coding, storing, and recalling our flickering thoughts. In short, it’s biology’s computer.”
Quantum Leaps
For ten years, when he hasn’t been escorting people in and out of consciousness, Hameroff has been modeling tubulin arrays on his computer, searching for some sort of code and signaling mechanism. “Do you have a minute?” He crooks a finger and then he’s careening down the hallway, like a New Yorker on his lunch hour, to the media instruction lab where he’s asked a biological illustrator to create an animated cartoon of flexing microtubules for the upcoming consciousness conference.
As it plays, Hameroff narrates, excited to see the world that has lived for so long in his imagination perform in living color, even if it is only a cartoon. “Each microtubule is a hollow cylindrical tube with an outside diameter of about twenty-five nanometers and an inside diameter of fourteen nanometers. Each tubulin dimer is about eight nanometers by four nanometers by four nanometers, and consists of two parts, alpha-tubulin and beta-tubulin, each made up of about four hundred fifty amino acids.”
In the cartoon, a single dimer is pulled out and magnified—it looks like a C character in the fat outline font. “At the elbow of the C, the junction of the alpha-tubulin and the beta-tubulin, there is a hydrophobic [water-fearing] pocket. In this pocket, an electron moves up and down in a metronome ticktock fashion called dipole oscillation. As it oscillates, it changes the shape of the protein, crimping the C and then stretching it.”
As we watch, cartoon beads of anesthesia gas start infiltrating from screen left. “Count backward from one hundred,” mumbles Hameroff. The minute the gas beads reach the dancing dimer bean, the electron in the pocket freezes, and the dancing stops. “Good-bye consciousness,” he announces.
Based on his own observations, Hameroff now believes that the electron freeze is caused by anesthetic molecules jamming into the hydrophobic space at the elbow of the C and binding there. When the electron stops oscillating, we lose consciousness.
But it’s not just the consciousness of higher animals that is affected by gas. Anesthesia can also stop the movement of paramecia, amoebae, and green slime molds, all of which rely on cytoskeleton for their oozing-forward movement. Hameroff knew that electrons acting alone inside each tubulin couldn’t possibly account for something as coordinated as a paramecium moving to catch its prey, let alone a conscious thought. Somehow, he theorized, the oscillating electrons must cooperate in a larger signaling and communication network. To find a plausible mechanism, Hameroff looked to a theory of computation known as cellular automaton theory.
A cellular automaton computer is a software program that sets up a grid of squares or “cells” (the spreadsheet kind, not the living kind). Each cell has a definite number of neighbors and has a formula of sorts embedded in it. The formula is called a transition rule. At discrete time intervals, a kind of musical chairs occurs. Every cell must check out the status of all of its neighbors and then change states—either on or off—according to its transition rule. A rule may state: If at least four of my six neighbors are “on,” I’ll be on too. Otherwise I’ll stay off. At each tick of the computer’s clock, the cells check out their neighbors and change on or off accordingly. It helps to think of the “on” squares as white and the “off” squares as black.
Amazingly, simple rules and a clock regulating the action lead to regular patterns of white and black developing and moving across the grid, in the same way that “The Wave” can propagate through a crowded stadium of strangers. With more complex rules, a cellular automaton in three dimensions could simulate the formation of a snowflake, mollusk shell, or galaxy. In fact, John von Neumann, known as the father of modern computing, suggested in the 1950s that such a lattice could be programmed to solve any problem. Learning this, Hameroff wondered, could microtubules be doing something like The Wave on their latticework of tubulin? Could they somehow be computing?
The illustrator fast-forwards the computer animation to a functioning array of microtubules. For this demonstration, he’s slit the soda straw of a microtubule lengthwise and unfurled it flat into a rectangular array. Each C-shaped tubulin is resting in spoon formation with its neighbors, so that the state of each dimer (whether its electron is up or down in the pocket) could be affected by the electrostatic state of its six neighbors. He hits PLAY, and an excited vibration begins in a patch of the array at one corner and ripples across the array like the energy of a wave moving through water. But it doesn’t stop there.
Hameroff believes that a microtubule can “catch” the oscillation of its neighbors—that is, a set of proteins vibrating in one microtubule could start another set vibrating in exactly the same way, like a tuning fork starting to vibrate in response to another in the same room. This “catching” oscillation, says Hameroff, may be possible because of a very unusual set of qualities that make microtubules the perfect substrate for quantum coherence.
“Coherence” is a hyper-organizing that imparts a strange and often wonderful quality to ordinary matter. When the crystals in a laser rod are pumped with enough energy, for instance, they will all of a sudden vibrate in lockstep fashion, and give off coherent laser light. Or when the linked electrons in a metal take on identical quantum characteristics, they become nearly frictionless conductors (a phenomenon called superconductivity). In supermagnets, microdipoles align, and in superfluids like helium, quantum-synchronized atoms create a friction-free fluid. But superconductors, supermagnets, and superfluids typically require temperatures near absolute zero to dampen thermal noise and bring their particles into alignment. The question is, can coherence happen in biological materials, at bodylike temperatures?
In the 1970s, Herbert Fröhlich of the University of Liverpool postulated that electrons trapped in the hydrophobic pocket of a protein like tubulin could oscillate, causing the protein to change shape in a predictable way. Further, he predicted that these electrons would oscillate coherently if they were in a uniform electromagnetic field (such as the walls of a microtubule) and were pumped with enough energy (provided by the bond severing of molecules like ATP or GTP). At some point, a s
et of proteins could reach a critical level of excitation and all of a sudden align in lockstep.
Applied to the microtubule, Hameroff postulated that the pattern of oscillation could either travel in waves, rippling across the lattice, or jump to nearby microtubules. These traveling shape-changes could allow signals to be carried throughout the neuron—signals that could direct, for instance, the movement of cilia or even the regulation of synaptic strengths. But how far could this coherence reach? If it could spread microtubule to microtubule, could it also go outside the neuron’s walls?
Consciousness, a brain-wide phenomenon, cannot be isolated to a neuron or two. In order to explain the “unified sense of self,” microtubules would need some way of coordinating their actions across large distances in the brain. To explain unity of self, Hameroff wandered even farther into the labyrinth of quantum mechanics.
As part of his exploration, he read a book by Roger Penrose called The Emperor’s New Mind, in which Penrose found quantum theory a thoroughly plausible explanation for how thoughts can appear to be magically distributed or “floating above” the brain, and yet still be anchored in matter. According to Penrose, if we could find the biological player in this quantum dance, we might be able to explain the unified sense of self.
Quantum mechanics applies to the very small things in our world, the substructure that underlies the visible world. In the early decades of the century, when quantum mechanics was first taking shape as a theory, it completely upended our ideas of physical reality. Newtonian laws were not completely banished—they still applied in our visible world—but they were no longer the be all and end all. Newton had no idea how weird the world of the tiny could be.
Two relevant legs of the quantum theory are the “superposition of states” and “quantum knowing.” The theory of superposition says that atoms are in many possible states simultaneously. They are searching among the various alternative energy states (an effect Michael Conrad called “quantum scanning”), and they don’t “choose” a state until they collide with matter or are observed. The famous argument in support of this is provided by the double-slit experiment, in which a low-intensity beam of photons is projected onto a wall punctured with two vertical slits. Behind the wall is a screen. Because the intensity is low and the photon stream is “dilute,” each photon should pass through one slit or the other. Instead, the pattern on the screen suggests that each photon passes through both slits at once. The bizarre but oft-replicated experiment seems to suggest that a photon can be in two places simultaneously.
Quantum theory says the photon is not just in those two places, but in many others as well. Scientists decided the best way to talk about a photon’s location would be to imagine a three-dimensional graph of all possible states. This is called the state space, and the “wave function” is a way of characterizing all the possible states that the photon may be in. Amazingly, when a particle comes into contact with matter—the molecules on the screen in the famous two-slit experiment, for instance—the wave function “collapses” to a single point, and the photon is forced to choose a single state to be in. When we observe something, we don’t see all its possible states—we see only one. We force it to be in only one state through the act of seeing or measuring it.
Michael Conrad has suggested that biological molecules exploit this freedom to shuffle the deck of many possibilities and explore possible solutions to, for instance, the problem of shape-based docking. In his view, enzymes are physically flopping around just before docking, and an electron tries out many different bonds, searching for a minimum energy configuration. Penrose postulated that our creative minds may play with possibility space in the same way—trying out dozens of different options simultaneously until one emerges as a conscious thought—a decision about what state to be in.
The second quantum theory that seems to relate to “mind” is the idea of quantum knowing. This states that movements of atoms, electrons, or other quantum particles may, under certain instances, be synchronized at great distances. As Hameroff writes, “The greatest surprise to emerge from quantum theory is quantum inseparability or nonlocality which implies that all objects that have once interacted are in some sense still connected! Erwin Schrödinger, one of the inventors of quantum mechanics, observed in 1935 that when two quantum systems interact, their wave functions become ‘phase entangled.’ Consequently, when one system’s wave function is collapsed, the other system’s wave function, no matter how far away, instantly collapses too.”
Talk about a truly interconnected world! Naturally, quantum knowing has been applied to many theories of cognition, including the holographic model of consciousness. Quantum knowing says that once two particles have been entangled quantumly, been part of the same quantum wave function, they are always related in some way—they know what their coherent relative is doing. In a sense they are their correlate particle. This means the same coherence that causes patterns to oscillate in synchrony inside the microtubule may cause coherence to occur in quantum relatives clear across the brain (or across brains!), without the need for neurons to be touching. Perhaps this same quantum knowing may account for such “supernatural phenomena” as Jungian collective unconscious, Hegel’s world spirit, and the strange ESP that you feel with a loved one who is miles away.
At the time he wrote Emperor, Penrose had the quantum arguments for consciousness worked out, but knew of no biological mechanism in the brain that would be capable of such quantum effects. He speculated that quantum effects in the brain would require a structure that was 1) small enough to be driven by quantum effects and 2) separated from the thermal hubbub of the rest of the brain. When Hameroff read these words, he found himself talking back to the pages. Tubulin proteins were small enough to host the quantum effects Penrose so beautifully described, and the hydrophobic cages inside the fibrils would indeed be a safe haven from the rest of the brain! He was ecstatic. “Penrose had handed me the quantum argument that I had been searching for, and I believed I was holding the missing biological piece that he needed.”
Hameroff wrote to Penrose and asked to come and see him. At a famous two-hour mindmeld at Penrose’s Oxford office, the two exchanged the missing pieces of the conceptual locket each had been carrying around. A few weeks later, Penrose stood up at a meeting and postulated that the microtubule may be the physical seat of consciousness.
In his latest book, Shadows of the Mind, Penrose lays out his arguments in a formal way. He believes that “mind” is a “macroscopically coherent quantum wave function” in the brain that is protected from entanglement with the thermal environment. The wave function is composed of quantum-connected electrons sitting in superposition—at both the upper and lower position of the hydrophobic pocket of each protein dimer. Because the pulse of vibrational energy in a microtubule is separated from the hubbub of the brain, it isn’t forced to choose a single state, and is free to investigate all possible patterns.
Penrose and Hameroff believe the microtubules’ almost crystalline structure may allow them to support a superposition of coherent quantum states for as long as it takes to do “quantum computing.” When the quantum superposition finally collapses, it triggers a spontaneous release of neurotransmitters (microtubules also direct this process). With this release, a thought, image, or feeling occurs to us. At this point they are trying to figure out how many neurons it would take for a conscious event—a collapse—to occur. They think the number may be ten thousand cooperating neurons.
As if coherence and cellular automata are not enough, Hameroff has entertained some half dozen other theories about how signals may be bounced around the brain on the trampoline of tubulin. Another theory imagines that the hollow tubes act as waveguides, like little fiber-optic cables. The water within the tubes structures in such a way as to emit a photon, which bounces along the waveguides, creating a tiny optical computer within our cells. Cytoskeletons may also be using soliton waves, sliding motions, coupling of calcium concentrations to cytoplasmic sol
-gel states, or constant polymerizing and depolymerizing to process signals.
Regardless of how microtubules are computing and communicating, Hameroff is convinced that they are, and he thinks if we let microtubules assemble themselves in a laboratory, we could get them to compute for us. “The neat thing about microtubules,” he tells me, “is that they can function outside of their cellular home [like BR can]. Put tubulin subunits in the right solution and they do what comes naturally—they self-assemble into beautiful cylinders cross-linked with MAPS. That means we could conceivably grow arrays of them in vats and use them as signaling media. We could use them as a storage device or even as an intelligent processor.”
Michael Conrad is also interested in this cellular trellis that so recently showed its face under our microscopes. “Chances are that microtubules will be a part of the tactilizing processor someday,” says Conrad. “Using their tiny centipedelike arms, they could push or pull the shapes, speeding them toward one another for self-assembly into a mosaic. Cytoskeletons could even be part of the readout mechanism. Instead of forming a mosaic, the floating shapes could somehow influence the self-assembly of cytoskeleton. The final shape of the cytoskeleton would reflect the pattern of inputs to the neuron [it would say “snowshoe hare”], and the readout enzymes would interpret the cytoskeleton instead of the mosaic. Finally, you could hook microtubules into long strands that act as physical transmission lines—wires—to connect tactilizing processors to one another in complex parallel networks.”
For Conrad, the cytoskeleton is like having a new multitalented personality join the team. “Think of all the processes that cytoskeletons may employ—conformational change, dipole oscillations, sliding motions, soliton waves, vibratory motions, sound waves, polymerization and depolymerization! This gives the system a lot of dynamics to work with, a lot to choose from when evolving a more efficient way to compute. Our idea is to feed evolution all the flexibility we can, and then stand out of its way and let it seek its own opportunities.”
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